In 1793 Spanish officials in St. Louis named Louis Lorimier the Commandant of the District of Cape Girardeau. Shortly thereafter, he reveived Spanish land grants totaling several thousand arpents (1 arpent = .85 acres). In 1806 Lorimier and his secretary, Barthelemi Cousin, laid out lot and street plans along the wide, flat riverfront. In 1808 the small riverfront village was incorporated as the town of Cape Girardeau.

An exciting incident occurred at the Battle of Cape Girardeau on April 23, 1863, when Confederate forces attacked from the west and south of town. During the battled several Confederate cannon balls pierced the roof of the residence of Alfred Lacey on Caruthers Street. Ike, a family slave, extinguished the resulting flames in the midst of the battle, saving the house from destruction.